Modulation of Ca2+ mobilization by protein kinase C in rat submandibular acinar cells

✍ Scribed by Ann-Christin Mörk; Guo H. Zhang; J. Ricardo Martinez

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 163 KB
• Volume: 72
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19990101)72:1<47::aid-jcb6>3.0.co;2-i

✦ Synopsis

The effects of protein kinase C (PKC) activation and inhibition on the inositol 1,4,5-trisphosphate (IP 3 ) and cytosolic Ca 2ϩ ([Ca 2ϩ ] i ) responses of rat submandibular acinar cells were investigated. IP 3 formation in response to acetylcholine (ACh) was not affected by the PKC activator phorbol 12-myristate 13-acetate (PMA), nor by the PKC inhibitor calphostin C (CaC). The ACh-elicited initial increase in [Ca 2ϩ ] i in the absence of extracellular Ca 2ϩ was not changed by short-term (0.5 min) exposure to PMA, but significantly reduced by long-term (30 min) exposure to PMA, and also by pre-exposure to the PKC inhibitors CaC and chelerythrine chloride (ChC). After ACh stimulation, subsequent exposure to ionomycin caused a significantly (258%) larger [Ca 2ϩ ] i increase in CaC-treated cells than in control cells. However, pre-exposure to CaC for 30 min did not alter the Ca 2ϩ release induced by ionomycin alone. These results suggest that the reduction of the initial [Ca 2ϩ ] i increase is due to an inhibition of the Ca 2ϩ release mechanism and not to store shrinkage. The thapsigargin (TG)-induced increase in [Ca 2ϩ ] i was significantly reduced by short-term (0.5 min), but not by long-term (30 min) exposure to PMA, nor by pre-exposure to ChC or CaC. Subsequent exposure to ionomycin after TG resulted in a significantly (70%) larger [Ca 2ϩ ] i increase in PMA-treated cells than in control cells, suggesting that activation of PKC slows down the Ca 2ϩ efflux or passive leak seen in the presence of TG. Taken together, these results indicate that inhibition of PKC reduces the IP 3 -induced Ca 2ϩ release and activation of PKC reduces the Ca 2ϩ efflux seen after inhibition of the endoplasmic Ca 2ϩ -ATPase in submandibular acinar cells.